The object of the proposed investigation is to study the antigen-independent and antigen-dependent maturation of B lymphocytes. In the first case, we will study the sequence of events in which immature precursor cells in the bone marrow give rise to mature virgin B cells in the peripheral lymphoid tissues. In the second, we will study the dual pathways of antigen-dependent differentiation which generate antibody forming cells on one hand, and memory B lymphocytes on the other. Parameters used to determine maturation events, and to define B cell subpopulations, are cell surface markers (isotype pattern of cell surface immunoglobulin, Ia antigen, etc.), immune function (ability to transfer the adoptive primary and secondary antibody response in vivo and in vitro), and certain physiological characteristics (migration pattern, tissue distribution, cell size, etc.). One of our main goals is to determine the relationship between B cell surface IgD receptors, and the capacity to generate memory B cells. Methods used in these studies include immunofluorescent staining of B cell surface markers, and isolation of purified cell populations using the fluorescence activated cell sorter. The function of the purified cells is tested in adoptive transfer experiments which measure the ability of the cells to generate antibody forming cells and memory B cells. We are also studying the mechanism by which mitogens stimulate the secretion of IgM by a spontaneous B cell murine lymphoma (BCL1) bearing surface IgM and IgD.